Turki Abrar, Ueda Keiko, Cheng Barbara, Giezen Alette, Salvarinova Ramona, Stockler-Ipsiroglu Sylvia, Elango Rajavel
BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
Department of Pediatrics and.
J Nutr. 2017 Feb;147(2):211-217. doi: 10.3945/jn.116.240218. Epub 2017 Jan 4.
Phenylketonuria is characterized by mutations in the Phe hydroxylase gene that leads to the accumulation of Phe in plasma and the brain. The standard of care for phenylketonuria is nutritional management with dietary restriction of Phe and the provision of sufficient protein and energy for growth and health maintenance. The protein requirement in children with phenylketonuria is empirically determined based upon phenylketonuria nutritional guidelines that are adjusted individually in response to biochemical markers and growth.
We determined dietary protein requirements in children with phenylketonuria with the use of the indicator amino acid oxidation (IAAO) technique, with l-[1-C]Leu as the indicator amino acid.
Four children (2 males; 2 females) aged 9-18 y with phenylketonuria [mild hyperphenylalanemia (mHPA); 6-10 mg/dL (360-600 μmol/L)] were recruited to participate in ≥7 separate test protein intakes (range: 0.2-3.2 g ⋅ kg ⋅ d) with the IAAO protocol with the use of l-[1-C]Leu followed by the collection of breath and urine samples over 8 h. The diets were isocaloric and provided energy at 1.7 times the resting energy expenditure. Protein was provided as a crystalline amino acid mixture based on an egg protein pattern, except Phe and Leu, which were maintained at a constant across intakes. Protein requirement was determined with the use of a 2-phase linear-regression crossover analysis of the rate of l-[1-C]Leu tracer oxidation.
The mean protein requirement was determined to be 1.85 g ⋅ kg ⋅ d (R = 0.66; 95% CI: 1.37, 2.33). This result is substantially higher than the 2014 phenylketonuria recommendations (1.14-1.33 g ⋅ kg ⋅ d; based on 120-140% above the current RDA for age).
To our knowledge, this is the first study to directly define a quantitative requirement for protein intake in children with mHPA and indicates that current protein recommendations in children with phenylketonuria may be insufficient. This trial was registered at clinicaltrials.gov as NCT01965691.
苯丙酮尿症的特征是苯丙氨酸羟化酶基因突变，导致苯丙氨酸在血浆和大脑中蓄积。苯丙酮尿症的标准治疗方法是营养管理，限制饮食中的苯丙氨酸，并提供足够的蛋白质和能量以促进生长和维持健康。苯丙酮尿症患儿的蛋白质需求量是根据苯丙酮尿症营养指南凭经验确定的，该指南会根据生化指标和生长情况进行个体化调整。
我们使用指示剂氨基酸氧化（IAAO）技术，以L-[1-¹³C]亮氨酸作为指示剂氨基酸，确定苯丙酮尿症患儿的膳食蛋白质需求量。
招募了4名年龄在9至18岁的苯丙酮尿症患儿（2名男性；2名女性）[轻度高苯丙氨酸血症（mHPA）；6 - 10mg/dL（360 - 600μmol/L）]，采用IAAO方案，使用L-[1-¹³C]亮氨酸，参与≥7次不同的试验性蛋白质摄入量测试（范围：0.2 - 3.2g·kg⁻¹·d⁻¹），随后在8小时内收集呼气和尿液样本。饮食热量相等，提供的能量为静息能量消耗的1.7倍。蛋白质以基于鸡蛋蛋白模式的结晶氨基酸混合物形式提供，除苯丙氨酸和亮氨酸外，其摄入量保持恒定。使用L-[1-¹³C]亮氨酸示踪剂氧化速率的两阶段线性回归交叉分析来确定蛋白质需求量。
确定平均蛋白质需求量为1.85g·kg⁻¹·d⁻¹（R = 0.66；95%CI：1.37，2.33）。这一结果显著高于2014年苯丙酮尿症建议量（1.14 - 1.33g·kg⁻¹·d⁻¹；基于比当前年龄组推荐膳食摄入量高出120 - 140%）。
据我们所知，这是第一项直接确定mHPA患儿蛋白质摄入量定量需求的研究，表明目前苯丙酮尿症患儿的蛋白质建议量可能不足。该试验已在clinicaltrials.gov上注册，注册号为NCT01965691。
